Modeling brain dynamics in brain tumor patients using the virtual brain

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance

Coupled non-parametric shape and moment-based inter-shape pose priors for multiple basal ganglia structure segmentation

This paper presents a new active contour-based, statistical method for simultaneous volumetric segmentation of multiple subcortical structures in the brain. In biological tissues, such as the human brain, neighboring structures exhibit co-dependencies which can aid in segmentation, if properly analyzed and modeled. Motivated by this observation, we formulate the segmentation problem as a maximum a posteriori estimation problem, in which we incorporate statistical prior models on the shapes and inter-shape (relative) poses of the structures of interest. This provides a principled mechanism to bring high level information about the shapes and the relationships of anatomical structures into the segmentation problem. For learning the prior densities we use a nonparametric multivariate kernel density estimation framework. We combine these priors with data in a variational framework and develop an active contour-based iterative segmentation algorithm. We test our method on the problem of volumetric segmentation of basal ganglia structures in magnetic resonance (MR) images. We present a set of 2D and 3D experiments as well as a quantitative performance analysis. In addition, we perform a comparison to several existent segmentation methods and demonstrate the improvements provided by our approach in terms of segmentation accuracy

State of the Art of Level Set Methods in Segmentation and Registration of Medical Imaging Modalities

Segmentation of medical images is an important step in various applications such as visualization, quantitative analysis and image-guided surgery. Numerous segmentation methods have been developed in the past two decades for extraction of organ contours on medical images. Low-level segmentation methods, such as pixel-based clustering, region growing, and filter-based edge detection, require additional pre-processing and post-processing as well as considerable amounts of expert intervention or information of the objects of interest. Furthermore the subsequent analysis of segmented objects is hampered by the primitive, pixel or voxel level representations from those region-based segmentation. Deformable models, on the other hand, provide an explicit representation of the boundary and the shape of the object. They combine several desirable features such as inherent connectivity and smoothness, which counteract noise and boundary irregularities, as well as the ability to incorporate knowledge about the object of interest. However, parametric deformable models have two main limitations. First, in situations where the initial model and desired object boundary differ greatly in size and shape, the model must be re-parameterized dynamically to faithfully recover the object boundary. The second limitation is that it has difficulty dealing with topological adaptation such as splitting or merging model parts, a useful property for recovering either multiple objects or objects with unknown topology. This difficulty is caused by the fact that a new parameterization must be constructed whenever topology change occurs, which requires sophisticated schemes. Level set deformable models, also referred to as geometric deformable models, provide an elegant solution to address the primary limitations of parametric deformable models. These methods have drawn a great deal of attention since their introduction in 1988. Advantages of the contour implicit formulation of the deformable model over parametric formulation include: (1) no parameterization of the contour, (2) topological flexibility, (3) good numerical stability, (4) straightforward extension of the 2D formulation to n-D. Recent reviews on the subject include papers from Suri. In this chapter we give a general overview of the level set segmentation methods with emphasize on new frameworks recently introduced in the context of medical imaging problems. We then introduce novel approaches that aim at combining segmentation and registration in a level set formulation. Finally we review a selective set of clinical works with detailed validation of the level set methods for several clinical applications

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Shape Priors in Medical Image Analysis: Extensions of the Level Set Method

The 3D medical image segmentation problem typically involves assigning labels to 3D pixels, called voxels, which comprise a given medical volume. In its simplest form the segmentation problem involves assigning the labels part of the structure of interest or not part of the structure to each voxel using locally measured properties and prior knowledge of human anatomy. Robust segmentation remains an open research problem today due to the significant challenges in the task including: partial volume averaging, overlapping intensity distributions and image noise. In the face of these challenges prior knowledge needs to be added to make the segmentation methods more robust. Active contours were introduced in the late 1980\u27s mainly to address situations in which the object to be segmented had a single closed boundary. To address situations in which the object(s) to be segmented have unknown topology the level set framework was recently introduced to segment medical images. Unlike active contours, the level set method relies on an implicit shape representation rather than an explicit shape representation and hence new methods to impose prior knowledge about expected shape have to be devised for the new framework. This paper explores recent segmentation methods from four research groups which address the task of imposing prior knowledge of shape for object boundary segmentation. Three of the methods impose priors onto the level set technique and one employs a medial axis shape representation and Statistical shape information to guide a model-based segmentation. All of the methods include a notion of a statistical shape distribution. Each method is described, analyzed for its strengths and weaknesses. The paper concludes with a comparison of all four methods and recommendations for their applicability

Placental Flattening via Volumetric Parameterization

We present a volumetric mesh-based algorithm for flattening the placenta to a canonical template to enable effective visualization of local anatomy and function. Monitoring placental function in vivo promises to support pregnancy assessment and to improve care outcomes. We aim to alleviate visualization and interpretation challenges presented by the shape of the placenta when it is attached to the curved uterine wall. To do so, we flatten the volumetric mesh that captures placental shape to resemble the well-studied ex vivo shape. We formulate our method as a map from the in vivo shape to a flattened template that minimizes the symmetric Dirichlet energy to control distortion throughout the volume. Local injectivity is enforced via constrained line search during gradient descent. We evaluate the proposed method on 28 placenta shapes extracted from MRI images in a clinical study of placental function. We achieve sub-voxel accuracy in mapping the boundary of the placenta to the template while successfully controlling distortion throughout the volume. We illustrate how the resulting mapping of the placenta enhances visualization of placental anatomy and function. Our code is freely available at https://github.com/mabulnaga/placenta-flattening .Comment: MICCAI 201

A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed locally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The generative model is first estimated on a control population, then, for each subject, the markers are computed for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolution. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are more located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quiet high. In this context, the model can be used to generate plausible morphological trajectories associated with the disease. Our method gives two interpretable scalar imaging biomarkers assessing the effects of aging and disease on brain morphology at the individual and population level. These markers confirm an acceleration of apparent aging for Alzheimer's subjects and can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.Comment: NeuroImage, Elsevier, In pres

Laminar fMRI in Auditory Cortex at 7T

Auditory cortex is involved in the perception, attention, memory and imagery of sounds. Neuroimaging has been a rich source of information on which cortical areas are recruited for different tasks. However, a more detailed understanding has been confined to animal studies using invasive imaging modalities, and high-resolution functional descriptions of auditory cortex, including columnar/laminar specific activity, topographical organization within layers, and the way these representations transfer between processing structures remain poorly understood in humans. We present 7T fMRI as a non-invasive tool for high-resolution functional imaging of human auditory cortex on the laminar scale. We describe MATLAB tools for optimizing a segmentation pipeline in BrainVoyager, and an analysis pipeline using an SPM to examine functional differences between cortical layers of auditory cortex. These differences are measured within the context of auditory memory maintenance, imagery, and tonotopy